Establishment of a bluetongue virus infection model in mice that are deficient in the alpha/beta interferon receptor

PLoS One. 2009;4(4):e5171. doi: 10.1371/journal.pone.0005171. Epub 2009 Apr 9.


Bluetongue (BT) is a noncontagious, insect-transmitted disease of ruminants caused by the bluetongue virus (BTV). A laboratory animal model would greatly facilitate the studies of pathogenesis, immune response and vaccination against BTV. Herein, we show that adult mice deficient in type I IFN receptor (IFNAR((-/-))) are highly susceptible to BTV-4 and BTV-8 infection when the virus is administered intravenously. Disease was characterized by ocular discharges and apathy, starting at 48 hours post-infection and quickly leading to animal death within 60 hours of inoculation. Infectious virus was recovered from the spleen, lung, thymus, and lymph nodes indicating a systemic infection. In addition, a lymphoid depletion in spleen, and severe pneumonia were observed in the infected mice. Furthermore, IFNAR((-/-)) adult mice immunized with a BTV-4 inactivated vaccine showed the induction of neutralizing antibodies against BTV-4 and complete protection against challenge with a lethal dose of this virus. The data indicate that this mouse model may facilitate the study of BTV pathogenesis, and the development of new effective vaccines for BTV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bluetongue / immunology*
  • Bluetongue / prevention & control
  • Bluetongue virus / genetics
  • Bluetongue virus / immunology*
  • Bluetongue virus / pathogenicity
  • Cell Line
  • Lung / pathology
  • Lung / virology
  • Lymph Nodes / pathology
  • Lymph Nodes / virology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptor, Interferon alpha-beta* / genetics
  • Receptor, Interferon alpha-beta* / immunology
  • Spleen / pathology
  • Spleen / virology
  • Survival Rate
  • Viral Vaccines / immunology


  • Viral Vaccines
  • Receptor, Interferon alpha-beta